全文获取类型
收费全文 | 222篇 |
免费 | 20篇 |
国内免费 | 2篇 |
专业分类
儿科学 | 4篇 |
妇产科学 | 9篇 |
基础医学 | 58篇 |
口腔科学 | 1篇 |
临床医学 | 17篇 |
内科学 | 83篇 |
神经病学 | 11篇 |
外科学 | 24篇 |
综合类 | 2篇 |
一般理论 | 1篇 |
预防医学 | 21篇 |
眼科学 | 1篇 |
药学 | 6篇 |
肿瘤学 | 6篇 |
出版年
2022年 | 4篇 |
2021年 | 8篇 |
2020年 | 2篇 |
2019年 | 9篇 |
2018年 | 6篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 4篇 |
2014年 | 11篇 |
2013年 | 4篇 |
2012年 | 16篇 |
2011年 | 27篇 |
2010年 | 7篇 |
2009年 | 21篇 |
2008年 | 13篇 |
2007年 | 21篇 |
2006年 | 10篇 |
2005年 | 14篇 |
2004年 | 10篇 |
2003年 | 16篇 |
2002年 | 14篇 |
2001年 | 1篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有244条查询结果,搜索用时 31 毫秒
11.
Hajime Orita Jonathan Coulter Colleen Lemmon Ellen Tully Aravinda Vadlamudi Susan M Medghalchi Francis P Kuhajda Edward Gabrielson 《Clinical cancer research》2007,13(23):7139-7145
PURPOSE: Fatty acid synthase (FAS) is overexpressed in many human cancers and is considered to be a promising target for therapy. However, in vitro use of previous generations of FAS inhibitors has been limited by severe, but reversible, anorexia in treated animals, which is thought to be related to a parallel stimulation of fatty acid oxidation by these agents. This study investigated pharmacologic inhibition of FAS using C93, a rationally designed molecule that inhibits FAS activity without affecting fatty acid oxidation in preclinical models of lung cancer. EXPERIMENTAL DESIGN: Activity of C93 on FAS and fatty acid oxidation was evaluated in cultured non-small cell lung cancer (NSCLC) cells. Antineoplastic activity of the compound, given orally or by i.p. injection, was evaluated in s.c. and orthotopic NSCLC xenografts. RESULTS: Our experiments confirm that C93 effectively inhibits FAS without stimulating fatty acid oxidation in lung cancer cells. More importantly, C93 significantly inhibits the growth of both s.c. and orthotopic xenograft tumors from human NSCLC cell lines without causing anorexia and weight loss in the treated animals. CONCLUSIONS: We conclude that inhibition of FAS can be achieved without parallel stimulation of fatty acid oxidation and that inhibition of tumor growth in vivo can be achieved without anorexia and weight loss. Thus, this therapeutic strategy holds promise for clinical treatment of cancers, including non-small cell lung cancer, the leading cause of cancer mortality in the United States and Europe. 相似文献
12.
13.
14.
Certain congenital disorders that are rare in the general population are quite common in individuals with trisomic conditions. For example, complete atrioventricular septal defect occurs in about 20% of individuals with Down syndrome, an approximately 500-fold increase in risk as compared to individuals without Down syndrome. Genetic variation on the chromosome involved in the trisomy may affect susceptibility to these trisomy-specific disorders. That is, increased dosage of a variant may be directly involved in increasing the risk of a disorder, or it may be indirectly involved by causing up- or downregulation of other genes. As in standard disomic gene-mapping, one can search for genes using linkage or association methods. Within association methods, one can consider case-control methods or family-based control methods such as the transmission disequilibrium test (TDT). Most gene-mapping methods need to be substantially redesigned for use with trisomic data. In this paper, we present a "trisomic TDT", a statistical method of testing for nonrandom transmission of alleles from parents to trisomic children. We demonstrate the method on a dataset of parent-child trios in which the child has Down syndrome. 相似文献
15.
Messer WB Vitarana UT Sivananthan K Elvtigala J Preethimala LD Ramesh R Withana N Gubler DJ De Silva AM 《The American journal of tropical medicine and hygiene》2002,66(6):765-773
Before 1989, dengue epidemiology in Sri Lanka was characterized by frequent transmission of all four dengue serotypes but a low incidence of dengue hemorrhagic fever (DHF). After 1989, cases of DHF dramatically increased. Here we present the results of epidemiologic studies conducted in Colombo, Sri Lanka before and after epidemic emergence of DHF in 1989. We compared the proportion of dengue cases among people with fever attending clinics from 1980 to 1984 and in 1997 and 1998 to determine if an increase in dengue transmission was associated with more DHF cases being reported. We also compared the relative distribution of dengue virus serotypes circulating in Colombo before and after the emergence of DHF. We detected no significant differences in dengue as a proportion of fever cases or in serotype distribution between the pre and post-DHF periods. We conclude that an increase in virus transmission or a change in circulating serotypes does not explain the epidemic emergence of DHF in Sri Lanka. 相似文献
16.
Venezuelan Equine Encephalitis (VEE) virus replicon particles (VRPs) encoding Borrelia burgdorferi Outer surface protein A (OspA) were evaluated for their ability to induce an immune response and provide protection from tick-borne spirochetes. VRPs expressing ospA that accumulated intracellularly (VRP OspA) or that was secreted from host cells (VRP tPA-OspA) were tested. Both VRP OspA and VRP tPA-OspA expressed ospA in immunized mice. Mice vaccinated with VRPs expressing secreted OspA produced significant amounts of anti-OspA antibodies, whereas VRPs expressing intracellular OspA were less immunogenic. The VRP method of delivery induced a Th1 type immune response unlike the recombinant OspA protein in Freund's adjuvant, which induced a mixed (Th1 and Th2) immune response. The VRP tPA-OspA construct induced an immune response that reduced the bacterial load in feeding Ixodes scapularis and blocked transmission to the host. These results indicate that VRPs are capable of providing protection against tick-borne B. burgdorferi, and potentially can be used for developing improved vaccines against Lyme disease. 相似文献
17.
Faden RR Dawson L Bateman-House AS Agnew DM Bok H Brock DW Chakravarti A Gao XJ Greene M Hansen JA King PA O'Brien SJ Sachs DH Schill KE Siegel A Solter D Suter SM Verfaillie CM Walters LB Gearhart JD 《The Hastings Center report》2003,33(6):13-27
If stem cells fulfill their therapeutic promise, moving them from the laboratory into the clinic will raise several concerns about justice. One concern is that, for biological reasons alone, stem cell‐based therapies might not be available for every patient who needs one. Worse, depending on how we address the problem of biological access, they might benefit primarily white Americans. We can avoid this outcome—although at a cost—by carefully selecting the stem cells we make available. 相似文献
18.
Thiagalingam A Campbell CR Boyd A Ross DL Kovoor P 《Pacing and clinical electrophysiology : PACE》2003,26(11):2146-2150
Radiofrequency ablation of the left ventricle using an endocardially placed electrode is unable to reliably create transmural lesions even with active electrode cooling. To produce deeper radiofrequency lesions, the authors developed and tested a prototype intramural needle ablation catheter that had a distal 1.1-mm diameter straight needle that could be advanced 12 mm into the myocardium. Freshly excised hearts from eight male sheep were perfused and superfused with oxygenated ovine blood. Ablations were performed for 60 seconds with the prototype catheter and a conventional 5-mm irrigated tip ablation catheter at target temperatures of 90 degrees C and 50 degrees C, respectively. The ablation lesions were bisected and stained with blue tetrazolium to assess lesion geometry. The irrigated tip ablation catheter required significantly more power than the intramural needle ablation catheter (37.7 +/- 7.3 vs 6.4 +/- 2.1 W, P < 0.01). Intramural needle lesions were significantly deeper (12.5 +/- 3.0 mm vs 8.3 +/- 2.1 mm, P < 0.01) but less wide (3.9 +/- 1.1 mm vs 11.5 +/- 2.0 mm, P < 0.01) than irrigated tip lesions. There was a high incidence of crater formation (74%), popping (45%), and myocardial charring (29%) during irrigated tip ablation; these phenomena were not observed during intramural needle ablation. The intramural needle ablation catheter creates significantly deeper but narrower lesions without evidence of tissue boiling. This technology may be particularly useful for ablation of ventricular tachycardia originating from regions where tissue depth is increased, like the ventricular septum. 相似文献
19.
20.
Dieter RS Nanjundappa A Lopez JJ 《Journal of the American College of Cardiology》2010,56(15):1264; author reply 1264-1264; author reply 1265